We have described suppression of the mixed lymphocyte reaction (MLR) in humans by thymus-derived (T) cells and soluble T-cell derived factors. Such suppression is highly specific for HLA-D products on MLR responder lymphocytes, and in one example is also specific for determinants on MLR stimulator cells. MLR suppression is rare in healthy individuals but is common in disorders such as Hodgkin's Disease and sarcoidosis. The goals of the proposed project are to localize the genes controlling the induction and effector phases of suppression, isolate T suppressor cells (Ts), immunochemically characterize T suppressor factor (TsF), identify the target of TsF, and assess the possible role of MLR suppressor T cells in human disease. Particular emphasis will be given to defining functionally distinct lymphocyte populations which may be involved in suppression (for example, effector and target cells). To this end, a variety of xeno and alloantisera will be tested for the capacity to selectively bind lymphocyte subpopulations. Spleen cells from mice immunized with Ts and TsF will be fused to murine myeloma cells in an effort to obtain monoclonal anti-Ts and anti-TsF antibodies. TsF will be characterized according to molecular weight, protein and carbohydrate content. Immunoabsorbent columns will be used to test for the presence of HLA products and/or immunoglobulin determinants in TsF. Finally, patients with Hodgkin's Disease and sarcoidosis will be studied in various stages of disease and treatment in order to assess the possible role of MLR suppressor T cells in such disorders.